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Development of inducible vectors for human gene therapy

Research Project

Project/Area Number 09671420
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionNagoya University

Principal Investigator

MIZUNO Masaaki  School of Medicine, Nagoya University Research Assistant, 医学部, 助手 (70283439)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Jun  School of Medicine, Professor, 医学部, 教授 (40158449)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsBRAIN TUMOR / INTERFERON / GENE REGULATION / Tet SYSTEM / HSP / AAV VECTOR
Research Abstract

We have promoted the development of inducible vectors for human gene therapy for 2 years. We investigated the antitumor efficacy on human glioma cells when human interferon-beta (IFN-beta) gene therapy using heat-inducible adeno-associated virus (AAV) vectors was combined with low-temperature hyperthermia. We constructed AAV vectors that contain human IFN-beta gene and were driven by heat shock protein 70B (HSP70B) promoter (AAV-hsp-IFN-beta). The AAV-hsp-IFN-beta produced a small amount of human IFN-beta at 37゚C, but the amount increased >2-fold by heating medium at 39゚C for 8 h. At that time, the antitumor efficacy also increased remarkably and further was much stronger than that of AAV-hsp-IFN-beta alone. We observed cell death of human glioma cells induced by AAV-hsp-IFN-beta or low-temperature hyperthermia or both of them by using video-enhanced contrast differential interference contrast (VBC-DIC) microscopy. Infection of AAV-hsp-IFN-beta induced apoptosis and combination of AAV-hsp-IFN-beta and low-temperature hyperthermia induced both necrosis and apoptosis on human glioma cells. The same results were shown in the case of liposomes containing heat-inducible plasmids Also, Tet system was useful.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Mizuno M et al: "Effect of human interferon-β gene transfer upon human glioma transplanted into nude mouse braininvolvesinduced natural killer cells." Cancer Immunol Immunother. 47. 227-231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi T et al: "Gene therapy of central nervous system tumors." Neurologia medico-chiruugica. 38. 763-771 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bucur N et al: "Growth inhibition of experimental glioma by human interferon-β superinduced by cationic liposomes entrapping polyinosilic:polycytidilic acid." Neurologia medico-chiruugica. 37. 739-746 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M et al: "Improvement of transduction efficiency of recombinant adeno-associated virus vector by entrapment in multilamellar liposomes." Jpn J Cancer Res. 89. 352-354 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M et al: "Adeno-associated Virus Vectors Containing the Herpes Simplex Virus-thymidine Kinase Gene Cause Complete Regression of Intracerebrally Implanted Human Gliomas in Mice." Jpn J Cancer Res. 89. 76-80 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta S et al: "Video-enhanced microscopic visualization of apoptotic cell death caused by anti-Fas antibody in living human glioma cells." Brain Tumor Pathol. 15. 19-21 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi T,Yoshida J,Takaoka T,Sadatomo T,Mizuno M,Kimura S.: "Enzyme immunoassay of gliloma cell tenascin secretion and augmentation by tumor necrosis factor-alpha" Neurologia medico-chirurgica. 37. 392-398 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi T,Yoshida J,Ishiyama J,Mizuno M.: "Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNFalpha) and liposome-entrapped rH-TNFalpha" Neurologia medico-chirurgica. 37. 719-722 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta S,Mizuno M,Takaoka T,Yoshida J.: "Augmentation of anti-Fas antibody-mediated apoptosis on human glioma cells by liposomes associated with the antibody." J Neuro-Oncology. 35. 7-11 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M,Yoshida J,Peter Colosi, and Gary J Kurtzman.: "Adeno-associated Virus Vectors Containing the Herpes Simplex Virus-thymidine Kinase Gene Cause Complete Regression of Intracerebrally Implanted Human Gliomas in Mice." Jpn J Cancer Res. 89. 76-80 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M,Yoshida J.: "Improvement of transduction efficiency of recombinant adeno-associated virus vector by entrapment in multilamellar liposomes." Jpn J Cancer Res. 89. 352-354 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bucur N,Mizuno M,Wakabayashi T,Yoshida J.: "Growth inhibition of experimental glioma by human interferon-beta superinduced by cationic liposomes entrapping polyinosilic : polycytidilic acid." Neurol Med Chir (Tokyo). 38. 469-474 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta S,Yoshida J,Yamamoto S,Uemura K,Wakabayashi T,Mizuno M,Sakurai T,Terakawa S.: "Video-enhanced microscopic visualization of apoptotic cell death caused by anti-Fas antibody in living human glioma cells." Brain Tumor Pathol.15. 19-21 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M,Yoshida J.: "Effect of human interferon-beta gene transfer upon human glioma transplanted into nude mouse brain involves induced natural killer cells." Cancer Immunol Immunother. 47. 227-232 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wakabayashi T,Mizuno M,Yoshida J.: "Gene therapy of central nervous system tumors." Neurol Med Chir (Tokyo). 38. 763-771 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mizuno M et al: "Effect of human interferon-β gene transfer upon human glioma transplanted into nude mouse brain involves induced natural killer cells." Cancer Immunol Immunother. 47. 227-231 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wakabayashi T et al: "Gene therapy of central nervous system tumors." Neurologia medico-chiruugica. 38. 763-771 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Bucur N et al: "Growth inhibition of experimental glioma by human interferon-β superinduced by cationic liposomes entrapping polyinosilic : polycytidilic acid." Neurologia medico-chiruugica. 7. 739-746 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuno M et al: "Improvement of transduction efficiency of recombinant adeno- associated virus vector by entrapment in multilamellar liposomes." Jpn J Cancer Res. 89. 352-354 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohta S et al: "Video-enhanced microscopic visualization of apoptotic cell death caused by anti-Fas antibody in living human glioma cells." Brain Tumor Pathol. 15. 19-21 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuno M et al: "Adeno-associated Virus Vectors Containing the Herpes Simplex Virus-thymidine Kinase Gene Cause Complete Regression of Intracerebrally Implanted Human Gliomas in Mice" Jpn J Cancer Res. 89. 76-80 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohta S et al: "Augmentation of anti-Fas antibody-mediated apoptosis on human glioma cells by liposomes associated with the anbtibody" J Neuro-Oncology. 35. 7-11 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Wakabayashi T et al: "Antitumor activity of recombinant human tumor necrosis factor-α (rH-TNFα)and liposome-entrapped rH-TNFα." Neurologia medico-chiruugica. 37. 739-746 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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